Disease of Hematopoietic and Lymphoid System

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Disease of Hematopoietic and Lymphoid System

• Tian Dong ping (???)
• Department of Pathology,
• Shantou University Medical College
• 2004/5-12

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Section 1 Introduction

• A. Hemopoietic Organs
• Bone Marrow,
• Liver, Spleen
• Lymph node
• Tonsil, etc

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Section twoLeukopenia

• Neutropenia(??????)
• Agranulocytosis(??????)
• 1000/uL 200-300/uL

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Section twoLeukopenia

• Etiology and Pathogenesis
• Inadequate granulopoiesis
• Accelerated removal or destruction

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Section twoLeukopenia??? ???

• Morphology
• 1.Marrow hypercellularity
• 2.a marked decrease in maturing granulocytic
  precursors in the marrow
• Clinical course
• Malaise chills and fever followed by marked
  weakness and fatigability

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Section twoReactive leukocytosis?????????

• 1.Infections mononucleosis
• 2.Reactive lymphadenitis
• acute nonspecific lymphadenitis
• chronic nonspecific lymphadenitis
• 3.Cat-scratch disease

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Section 2 Lymphooid neoplasmsMalignant Lymphomas

• Summary
• Concept Lymphomas are malignant tumor which
  origin from lymph node and other lymphoid tissue.
• Classification
• Two main groups
• 1 Hodgkins disease(10-20)
• 2 non- Hodgkins lymphoma
  (80-90).

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Malignant Lymphoma
Lymphocytic leukemia
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Certain important principles must be emphasized

• 1.80-85 is B Cell origin with T-cell tumors
  making up most of the remainder
• 2.Many tumor of mature B cell arise from and
  recapitulatethe follicular growth pattern of
  normal B cells
• 3.As tumors of the immune system, Lymphoid
  often disrupt normal immune regulatory mechanisms
• 4. All lymphoid neoplasms are derived from a
  single transformed cell and are therefore
  monoclonal.
• 5.Although NHLs often present as involvement of a
  particular tissue site, sensitive molecular
  assays usuall show that the tumors is widely
  disseminated at the time of diagnosis.

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Hodgkins Lymphoma(HL)Hodgkins Disease (HD)

• Hodgkins disease is disorder involving
  primarily the lymphoid tissue, the disease, which
  in the commonest type of lymphoma, may occur at
  any age but there are 2 peaks of incidence
• ? around adolescence.
• ? in late middle and older age.

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• Morphology
• Site the disease begins in a single lymph
  node (e. s. cervical) followed by spread to
  adjacent nodes and to other organs in a fairly
  consistent pattern.

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• Grossly
• single to multiples mass,
• gray-white-color,soft,uniform fish-flesh .
• yellow-white necrosis on the cut surface.

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• Microscopy
• 1. The normal architecture of lymph node has
  been destroyed and replaced by tumour tissue, the
  variety cells present in the tumour tissue.

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• 2.The one constant feature is the presence of
  Reed- Stern berg (RS) cells.
• ? Typical RS cell
• large cell 30-60µm dram. Amphophilic
  cytoplasm
• large nuclei two or more nuclei when the RS
  cell contain two large nuclei.
• We term it mirror image nuclei
• Large nucleoli the large eosinophilic
  nucleoli is character.

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• ? cells closely related to RS cell
• The lacunar cell shrinkage of cell cytoplasm
  towards cell wall and nucleus, leaving a clear
  space.
• Popcorn cell
• Mononuclear Hodgkins cell nuclear
  characteristic similar to RS cell but smaller.
  These cell are not specifically diagnostic of
  Hodgkins disease.

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• ? no tumors cells
• lymphocyte, plasma cells, necrophilia,
  eosinophilic cell et al.

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WHO??

• ???
• ??????????
• ???

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The Rye classification

• 1. Nodular Sclerosing (40)
• Thick bands of collage separating Hodgkins
  tissue lacunar cells often numerous (often
  mediastinal presentation)

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2. Mixed cellularity (25) Plasma cells and
eosinophils present in addition to RS cells and
lymphocytes.
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Hodgkin disease, mixed cellularity type.
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• 3. Lytnphocyte Depleted (15)
• Very numerous RS and mononuclear Hodgkins
  cells, few lymphocytes and some diffuse fibrosis.

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• 4. Lymphocyte predominant (5)
• Very numerous lymphocytes
• Scanty RS cell
• Divited into 2 types
• . Nodular type
• 2), Diffuse type

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Transtion from better to worse prognosis type
occurs 4? 2?3 but nodular sclerosing usually
remains true to type.---fibrosis
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• Complications
• The immunity function is lower (reduce)
• The patient easily suffer from infection of
  virous and fungus.

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The Non- Hodgkin lymphomas

• The non- Hodgkin lymphoma are solid tumours
  arising in the peripheral lymphoid tissue
  particularly of lymphnodes but also of the
  extranodal sites such as the oro- pharynx, the
  gut, skin and other sites.

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• Grossly The same as Hodgkins diseases but
  the mass is more soft and a few necrosis.
• The normal architecture of lymph node have been.
  Destroyed partly or entirely.
• Very numerous monotonous neoplastic cell flood
  in lymph node. The neoplastic cell may be
  infiltrate to the capsule of node.

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Classification

• 1. Rappaport classification
• The traditional classification is purely
  morphological criteria.
• The subset ? nodular type
• ? diffuse type
• Then according to differentiated degree of
  tumor cell again divided into several type
  (well, poorly, nodifferentiated)

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• 2. Lukes Collins classification
• The NHL are classificed into T cell, B cell
  and null cell, histiocytic categories by using
  immunologist and catechetical markers as adjuncts
  to morphology.

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Classification of The Non- Hodgkin lymphomas
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????????KIEL??
B??? T???
???? ????? ????????? ???????? ?????? ??????/?????? ???? ?????/????? ?????? ??? ?????(???) ?????,??????? ???? ?????? ?????? Burkitt??? ??????(Ki-1) ?????? ???? ????? ????????? ???????? ???,?? ?????,Sezary??? ????? ???????? T???? ???,????(HTLV-1 ) ???,???????(HTLV-1 ) ??????(HTLV-1 ) ??????(Ki-1 ) ?????? ????
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REAL??????????
B??? T???
??B????? ??B-????????/??? ??B????? ?????????/????????? ????????? ?????? ????????,??? ???????? ?????? ????/??? ??????B????? Burkitt??? ??T????? ??T-????????/??? ??T????? T?????????? ?????????? ?????/Sezary??? ??T???,??? ????????T????? ??????????(NK/T?????) ??T????? ??T?????/??? ?????????,T?null???
?????? ??????????
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WHO??????????? P229
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Complication and resulted

• Easily accompanied by virous and bacteria
  infection
• Single or group of nodes involved if no systemic
  manifestation occur, the progressive may be good.
• More advanced, evidence of extra nodal
  involvement is already present, live, spleen have
  been offended,
• in same time, patient feel no power, loss
  weights, anemia. The prognosis is poor.

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• Example of Malignant Lymphomas
• 1.Precursor B-and T-cell Lymphoblastic leukemia/
  lymphoma
• 2.Small lymphocytic lymphoma/chronic lymphocytic
• Follicular lymphoma
• Mantle cell lymphoma
• Diffuse large B-cell lymphoma
• Burkitt lymphoma
• Plasma cell dyscrasias
• Peripheral T-cell lymphoma
• Mycosis fungoides
• NK/T-cells lymphoma

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????????

• T?????CD2 CD3 CD4 CD7 CD8
• B?????CD10 CD19 CD20 Ig??
• NK????CD16 CD56
• ??????? TdT ??????????
• ????CD13 CD14 CD15 CD64
• ???CD34
• CDCluster of differentiation

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(1)Lymphoblastic Lymphoma?????????

• ??T?????B????
• ????
• ???????,????,??????,??????????,?????,??. ?????

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• ?????
• ????TdT() SIg(-)
• CD10,CD19()??B
• CD2,CD3,CD7()??T
• ???????gt50????
• t(1221), t(922)
• t(411)
• ????,???????

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• C. Result
• 5 year survival rate
• Low grade malignant 100
• Middle grade malignant 28
• High grade malignant 0

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• (2) Small lymphocytic lymphoma
• ????????

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• ????
• ?????????,?????????????????
• ????CD19,CD20,CD23()
• ????IgH?IgL????
• 30 12???
• ????

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• (3)Follicular lymphoma
• ??????

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• ???????
• ??????????
• ?????????
• ????????????
• ?????,????
• ?????????
• ???? CD19,CD20,CD10(),bcl-2()
• ???? t(1418)
• ?? ??

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• (4) Diffuse large B-cell lymphoma
• ????B?????

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• ????
• ???????,?????????????
• ???????,?????
• ????????,??
• ???? CD19,CD20()
• ???? 30 t(1418) bcl-2??
• ?? ??,?50????

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(5)Peripheral T-cell lymphoma, unspecific??T?????
,???

• ????
• ????????
• ???????,??????,??????????????????????????
• ????CD2,CD3,CD5()
• ????

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(6)NK/T Cell Lymphoma

• ????????,?????????,?????????
• ????
• ??????100
• ????????
• ?????????????????????
• ?????
• ????CD2,CD3,CD56()
• ????,????,????,???(???)??,?????,5???75?

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• (7) Burkitt lymphoma
• ??????
• ?????

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Burkitts lymphoma

• Brukitts lymphoma was described initially in
  Africa, where it is endemic in some parts, but it
  is also ocure sporadically in nonendemic area.
  Only very rare cases have been recorded in
  European and North America. This disorder is
  relationship of the Epstein-Barr viruses. Both
  the African and non Africa cases are found
  largely in children or young adults.

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• The disease rarely arises in lymph nodes, but
  usually appears in the jaw or ovaries
  (retroperitoneal tissues in males) this disease
  grows extremely rapidly and spreads extensively,
  leading quickly to complication.

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• Histological appearance is typical and
  striking
• 1. diffuse proliferation of lymphoblasts (B
  cell type) cell medium- sized and uniform,
  mitoses frequent.
• 2. Scattering of macrophages containing debris
  desired from very rapid cell turnover
  contributing starry sky. These benign
  macrophage are diffusely distributed among the
  tumor cell. The macrophage often sounded by a
  clear space.

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• Leukemic transformation may occur, but is
  uncommon, these tumors respond well to aggressive
  chemotherapy and long remissions have been
  reported. However, in most cases a relapse
  occurs, and a majority of patients die with in 5
  years.

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Burkitt lymphoma
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(8)Mycosis fungoides

• Mycosis fungoides are uncommon lymphoid
  malignancies that are primary in the skin. It is
  infrequent T cell lymphomas. These disease
  usually affects males 40-60 years of age.

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• Grossly The lesions begin as poorly defined
  areas of eczema, followed by formation of plaques
  and ultimately of multiple nodules. The nodules
  often rapture and become ulcer.

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• Histologically
• This disease is characterized by dermal
  infiltrates of atypical lymphoid cell that invade
  the epidermis. The neoplastic cell (mycosis
  cells) have deeply lobulated or cerebra-form
  nuclei. Immunology studies indicate the presence
  of T cell markers on mycosis cells.

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??????????????

• 1. ??????
• 2B-Cell ??.???? ---r ?
• 3.???????????????

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Section 4 Leukemia

• A. Definition
• Leukemia is malignant tumor of the
  hemotopoietic stem cell. In most cases, the
  leukemic cell infiltrate the blood, Liver,
  Spleen, Lymph node and other tissues.

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• B. Classification
• 1. According the clinic course
• Acute
• Chronic

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• 2. According to the Leukemic cell type
• Myelocytic
• Lymphocytic
• e.g 4 types
• AML (59), ALL (25.2), CML (12.1), CLL
  (1.9) shanhai

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Acute leukemia(AML) Acute myelogenous
leukemia(AML) Classfication M0,---minimally
differentiated AML(????) M1,--- AML without
differentiation(???) M2 --- AML with
differentiation(???) M3--- acut promyelocytic
leukemia(?????) M4---acut myelomonocytic
leukemia(?????) M5---acut monocytic
leukemia(????) M6---acut erythroleukemia(????) M7-
--Acute megakaryocytic leukemia(????)
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• C. Pathologic feature of acute leukemia
• 1. Peripheral blood
• WBC 20000-50000/µl
• Myeloblastic
• Lymphoblastic 30-90

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• 2. Bone marrow
• Normal marrow is diffuse replaced by leukemic
  cells. Bone marrow develop a muddy, red- brown to
  grey-white color. In AML, bone is infiltrated by
  tumor cell form tumorous mass, termed chloroma.

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• 3. Lymph node
• Enlargement, normal structure of LN is
  destroyed partly or entirely.

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• 4. Liver
• Enlargement middle degree. In ALL, Leukemic
  cell Infiltrates the portal areas, but in AML,
  Leukemic cell are present within the sinusoids
  throughout the lobule.

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• 5. Spleen
• Only moderate spleenmegaly, 500-1000gm. In AML
  Leukemic cells infiltrate to the red pulp and
  venous sinuses. In ALL, the white pulp is
  primarily involved. Ultimately the speen
  structure is obliterated.

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• D. Pathologic feature of chronic Leukemia
• 1. Peripheral Blood
• WBC 100000-800000 /µl
• The most cells are more mature forms.

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• 2. Bone Marrow
• BM proliferate actively, in CML the most of
  tumor cells are myelocyte and metamyelocyte. In
  CLL, the most of tumor cells are mature
  lymphocyte.

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• 3. Spleen
• Massive splenmegaly is character of CML 5000gm
  or more
• In CLL, between 500-1000gm
• In CML, numerous areas of pale infarction
• Leukemic cell infiltrate focal or diffuse,
  Ultimately the spleen structure is obliterated.

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• 4. Liver
• Its same as acute Leukemia

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• E. Result and Complication
• Progrosis is very poor.
• Survival period Acute Leukemia 36 mo.
• Chronic Leukemia 5
  years
• But all of patients would be died
• Cause of die
• 1. Infection 2. Hemorrhage
• 3. Organ function failure

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• C. Result
• 5 year survival rate
• Low grade malignant 100
• Middle grade malignant 28
• High grade malignant 0

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Section 5 Malignant Histiocytosis (M H)

• A. Definition
• M H is an aggressive and rapidly fatal
  systemic malignant tumor of the mononuclear
  phagocyte.

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???????

• ????????????????????
• ??---???????.
• ???----???????????
• ??---????????????

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??????????????????acute sisseminated Langerhans
cell histocytosis

• ?????????????????,??????????????,
• ???2?????????????-???????? ?? ??????---?--????
• ??,????,??????????50??5??

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?????? eosinophilic granuloma

• ????????????????
• ??,??, ????
• ?????,?????,???,??????
• ????????????????.????,????

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